Effect of MTTP -493G/T, I128T, Q95H and Q244E polymorphisms on hepatic steatosis in patients with chronic hepatitis

Background: Chronic hepatitis C is characterized by a progressive deterioration of liver function and is involved in metabolic complications, such as hepatic steatosis. Objective: The aim of this study was to investigate the role of host and viral characteristics associated with -493G/T (rs1800591), I128T (rs3816873), Q95H (rs61733139), and Q244E (rs17599091) Single Nucleotide Polymorphisms (SNPs) in the Microsomal Triglyceride Transfer Protein (MTTP) gene on hepatic steatosis in chronic hepatitis C. Methods: SNPs were genotyped by PCR-RFLP and analyzed in combination with host and viral characteristics by multiple logistic regression in different genetic models of inheritance. Results: The authors analyzed 236 patients with chronic hepatitis C, and 53% had hepatic steatosis. The mutated allele frequencies were > 5%, and the genotypes were in Hardy-Weinberg equilibrium (p ≥ 0.05). It was observed that patients with HCV genotype 3 infection (OR = 2.74, 95% CI 1.24‒6.06, p = 0.013), female sex (OR = 2.28, 95% CI 1.21‒4.28, p = 0.011) and moderate- and high-intensity liver inflammatory activity (A2-A3) (OR = 3.61, 95% CI 1.86‒7.01, p < 0.001) alone exhibited a higher risk of steatosis. The results of multiple logistic regression analysis for interaction showed that for the -493G/T SNP, when the GT/TT genotype (dominant model) and the GT genotype (codominant model) were each combined with HCV genotype 3 infection, an 11.51-fold (95% CI 2.08‒63.59, p = 0.005) and a 15.69-fold (95% CI 2.46‒99.85, p = 0.004) increased risk of steatosis, respectively, was observed. For the I128T SNP, when both the IT/TT genotype (dominant model) and the IT genotype (codominant model) were combined with HCV genotype 3 infection, an 8.51-fold (95% CI 1.59‒45.54, p = 0.012) and an 8.40 fold (95% CI 1.51‒46.91, p = 0.015) increased risk of steatosis, respectively, was observed. Conclusion: The present study showed that the viral genotype combined with the -493G/T and I128T SNPs in the MTTP gene influences hepatic steatosis

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Performance of non-invasive indirect biological markers for liver fibrosis assessment in patients chronically infected with hepatitis B virus, hepatitis C virus and coinfected with HCV and human immunodeficiency virus

Introdução: A lesão no fígado quando persistente pode levar à doença hepática crônica, cirrose e hepatocarcinoma (HCC). As hepatites virais causaram globalmente 1,34 milhões de mortes em 2015. No ano de 2019, o vírus da hepatite C (HCV) pelo mundo causou a morte de aproximadamente 820 mil e, o vírus da hepatite B (HBV) 290 mil pessoas, e as principais causas foram a cirrose e o HCC. O estudo anatomopatológico de fragmento hepático é o padrão ouro para avaliar e acompanhar o grau de fibrose nos pacientes com doença hepática. Novos métodos estão sendo desenvolvidos, tais como os marcadores não invasivos para avaliar a fibrose hepática. Os marcadores biológicos não invasivos indiretos são práticos, porém precisam ser validados com amostras de pacientes de outras regiões do mundo, além daquelas em que foram desenvolvidos. Objetivo: O objetivo deste estudo foi avaliar o desempenho dos marcadores não invasivos indiretos (APRI, FIB-4, Forns, Lok, GUCI e FibroIndex) para a fibrose hepática, comparando-os ao estudo anatomopatológico do fragmento hepático. Métodos: Trata-se de estudo retrospectivo de revisão de prontuário de pacientes atendidos no Ambulatório da Divisão de Clínica de Moléstias Infecciosas e Parasitárias do HCFMUSP. O resultado do estudo anatomopatológico do fragmento hepático pela classificação METAVIR foi utilizado para avaliar o desempenho dos marcadores não invasivos selecionados (APRI, FIB-4, Forns, Lok, GUCI e FibroIndex) em três grupos de pacientes: pacientes com infecção crônica pelo HBV, HCV e coinfecção HIV/HCV. O poder discriminativo de cada marcador foi comparado aos dados obtidos pelo estudo anátomo-patológico do fragmento hepático. Foram feitas análises do desempenho do marcador através do cálculo da sensibilidade, especificidade, razão de verossimilhança positivo e negativo e pela construção de curvas ROC (receiver operator characteristic) para a mensuração da área sob a curva (AUROC), demonstrando o poder discriminativo de cada marcador. Resultados: Dos marcadores não invasivos testados para o diagnóstico de lesão hepática relacionada ao HBV, o desempenho satisfatório (considerada quando AUROC > 0,8) para a fibrose avançada foi verificado pelo FibroIndex com AUROC de 0,809 e, para o diagnóstico de cirrose hepática o FibroIndex, APRI e GUCI foram considerados satisfatórios (AUROC de 0,855; 0,798 e 0,792, respectivamente). Para o diagnóstico de lesão hepática relacionada ao HCV, a fibrose significativa pode ser atendida pelos marcadores APRI (AUROC 0,804), GUCI (AUROC 0,805) e FIB-4 (AUROC 0,787). A AUROC satisfatória para avaliar a fibrose avançada foi verificada pelos marcadores APRI (0,833), FIB-4 (0,831), GUCI (0,833), FibroIndex (0,828) e pelo Forns (0,831) e para a presença de cirrose em nosso estudo, foi através do FIB-4 (0,922), FibroIndex (0,918), Forns (0,902), APRI (0,898), GUCI (0,898) e o LOK (0,841). Para o diagnóstico de lesão hepática relacionada à infecção concomitante pelo HCV/HIV a presença de fibrose significativa apresentou AUROCs satisfatórias com os marcadores GUCI (AUROC 0,83) e o APRI (AUROC 0,82). No diagnóstico de fibrose avançada foram: GUCI (AUROC 0,88), FibroIndex (AUROC 0,87), APRI (AUROC 0,861), LOK (AUROC 0,86) e o FIB-4 (AUROC 0,85). E no diagnóstico de cirrose o marcador LOK (AUROC 0,94), FIB-4 (AUROC 0,91), FibroIndex (AUROC 0,89), GUCI (AUROC 0,88), APRI (AUROC 0,86) e Forns (AUROC 0,86) se destacaram para diagnosticar estes pacientes. Conclusão: Este estudo concluiu que a avaliação da fibrose hepática, pelos marcadores não invasivos indiretos, é útil e pode ser realizada para os pacientes com hepatite B e C, e para àqueles coinfectados com HCV/HIV. Porém, validações são necessárias para adequar os valores dos pontos de corte para cada populaçãoIntroduction: Persistent liver injury can lead to chronic liver disease, cirrhosis, and hepatocellular carcinoma. Viral hepatitis caused 1.34 million deaths globally in 2015. The hepatitis C virus (HCV) caused the death of approximately 290,000 individuals and the hepatitis B virus (HBV) of approximately 820,000 individuals worldwide in 2019, and the main causes were cirrhosis and HCC. The anatomopathological study of liver fragments is the gold standard to assess, track and follow up the fibrosis stages in patients with liver disease. New methods are being developed, such as non-invasive biomarkers to assess liver fibrosis. Noninvasive indirect biomarkers are practical, but need to be validated with patient samples from other regions of the world, in addition to those in which they were developed. Objective: The aim of this study was to evaluate the performance of non-invasive indirect biomarkers (APRI, FIB-4, Forns, Lok Index, GUCI and FibroIndex) by comparing them with the anatomopathological study of the liver fragment in the assessment of liver fibrosis stage, in patients chronically infected with HBV, HCV and HIV/HCV coinfection. Methods: A retrospective study with medical records review of patients was conducted at the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP). The result of the anatomopathological study of the liver fragment, evaluated by the METAVIR classification, was assumed as the gold standard. We evaluated the performance of selected non-invasive markers (APRI, FIB-4, Forns, Lok Index, GUCI and FibroIndex) in three groups of patients: patients with chronic hepatitis B virus infection, patients with hepatitis C virus infection and patients with HIV/ HCV coinfection. The discriminative power of each marker was compared to the data obtained by the anatomopathological study of the liver fragment. The diagnostic performance of the markers was evaluated by sensitivity, specificity, positive and negative likelihood ratios and by building receiver operator characteristic (ROC) curves to measure the area under the curve (AUROC); and finally, demonstrating the discriminative power of each marker. Results: Of the non-invasive markers tested for the diagnosis of HBV-related liver injury, satisfactory performance (considered when AUROC >0.8) for advanced fibrosis was verified by FibroIndex with an AUROC of 0.809 and, for the diagnosis of liver cirrhosis by FibroIndex, APRI and GUCI was 0.855, 0.798 and 0.792, respectively. For the diagnosis of HCV-related liver injury, significant fibrosis (considered when AUROC >0.8) was verified by APRI (AUROC 0.804), GUCI (AUROC 0.805) and FIB-4 (AUROC 0.787) markers. An AUROC satisfactory to evaluate advanced fibrosis was verified by APRI (0.833), FIB-4 (0.831), GUCI (0.833), FibroIndex (0.828) and Forns (0.831) markers and, for the presence of cirrhosis by FIB-4 (0.922), FibroIndex (0.918), Forns (0.902), APRI (0.898), GUCI (0.898) and LOK (0.841). For the diagnosis of liver injury related to concomitant HCV/HIV infection, the presence of significant fibrosis showed satisfactory AUROCs by GUCI (AUROC 0.83) and APRI (AUROC 0.82) markers. For the diagnosis of advanced fibrosis, the markers that indicated AUROCs > 0.8 (satisfactory performances) were GUCI (AUROC 0.88), FibroIndex (AUROC 0.87), APRI (AUROC 0.861), LOK (AUROC 0.86) and FIB-4 (AUROC 0.85). And for the diagnosis of cirrhosis the markers LOK (AUROC 0.94), FIB-4 (AUROC 0.91), FibroIndex (AUROC 0.89), GUCI (AUROC 0.88), APRI (AUROC 0.86) and Forns (AUROC 0.86) stood out to diagnose these patients. Conclusion: This study concluded that hepatic fibrosis assessment by non-invasive indirect markers proved to be useful and can be performed for patients with hepatitis B and C, and for those coinfected with HCV/HIV. However, validations are necessary to adjust the cut-off values for different population

Seroprevalence of hepatitis C virus among people living with HIV/AIDS in Latin America and the Caribbean: a systematic review

Abstract Background Studies have shown that the immunosuppression induced by the human immunodeficiency virus (HIV) accelerates the natural history of liver disease associated with hepatitis C virus (HCV), with 3- to 5-fold higher odds of coinfected individuals developing cirrhosis. However, estimates of the seroprevalence of hepatitis C among people living with HIV/acquired immune deficiency syndrome (AIDS) (PLHA) in Latin America and the Caribbean (LAC) are widely variable. Methods We performed a systematic review to estimate the seroprevalence of HCV among PLHA. We searched studies on HIV and HCV infections in LAC included in the PubMed, LILACS and Embase databases in December of 2014 with no time or language restrictions. The following combinations of search terms were used in the PubMed and Embase databases: (HIV OR Acquired Immunodeficiency Syndrome Virus OR AIDS OR HTLV OR Human Immunodeficiency Virus OR Human T Cell) AND (HCV OR HEPATITIS C OR HEPATITIS C VIRUS OR HEPACIVIRUS) AND (name of an individual country or territory in LAC). The following search terms were used in the LILACS database: (HIV OR AIDS OR Virus da Imunodeficiencia Humana) AND (HCV OR Hepatite C OR Hepacivirus). An additional 11 studies were identified through manual searches. A total of 2,380 publications were located, including 617 duplicates; the remaining articles were reviewed to select studies for inclusion in this study. Results A total of 37 studies were selected for systematic review, including 23 from Brazil, 5 from Argentina, 3 from Cuba, 1 from Puerto Rico, 1 from Chile, 1 from Colombia, 1 from Mexico, 1 from Peru and 1 from Venezuela. The estimated seroprevalence of HCV infection varied from 0.8 to 58.5 % (mean 17.37; median 10.91), with the highest in Argentina and Brazil and the lowest in Venezuela and Colombia. Conclusions Investigation of HCV infection among PLHA and of HIV infection among people living with HCV is highly recommended because it allows for better follow up, counseling and treatment of HIV/HCV-coinfected patients. Future studies with larger sample sizes are needed in both South and Central America to understand and address the risk factors associated with the acquisition of infection

The rs738409 polymorphism of the PNPLA3 gene is associated with hepatic steatosis and fibrosis in Brazilian patients with chronic hepatitis C

Abstract Background Prospective studies have shown that 80% of acute hepatitis C virus (HCV) cases progress to chronic infection; approximately 10-20% of patients with these conditions will develop liver cirrhosis within 2 to 3 decades, and 1-5% will develop liver cancer. Some studies have indicated that the rs738409 polymorphism of the PNPLA3 gene is associated with steatosis and the progression of advanced fibrosis. This study assessed the contribution of the PNPLA3 rs738409 polymorphism with regard to the steatosis and degree of liver fibrosis in Brazilian patients diagnosed with chronic hepatitis C. Methods A total of 290 patients were evaluated at the Clinics Hospital of the School of Medicine, University of São Paulo, between 2010 and 2015. The inclusion criteria were age ≥ 18 years and positive anti-HCV antibody and HCV RNA tests. The participants were evaluated based on medical consultation, blood tests, and liver biopsies conducted before specific antiviral therapies were applied. The associations between the rs738409 PNPLA3 gene polymorphism and steatosis and advanced fibrosis were tested under a recessive inheritance model using logistic regression analysis, including age, gender, BMI, ethnicity/color, HOMA-IR, alcohol intake, HCV genotype 3, and the rs58542926 TM6SF2 gene polymorphism as covariates. Results The mean age of the patients was 54.9 years old (range, 28 to 82 years), and 124 (42.8%) patients were male; 226 (77.9%) were white, 43 (14.8%) were pardo, and 21 (7.2%) were black Brazilians. Of the patients included in this study, 133 (45.9%) presented with the CC genotype, 63 (21.7%) with the CG genotype, and 94 (32.4%) with the GG genotype of the PNPLA3 gene I148M variant. We observed that the associations between PNPLA3 rs738409 GG genotype and steatosis was significant (OR: 2.16; 95% CI 1.26-3.72). The same genotype was associated to advanced fibrosis too (OR:2.64; 95% CI 1.26-5.53). Conclusions Associations between the rs738409 polymorphism of the PNPLA3 gene genotype GG and hepatic steatosis and advanced fibrosis were observed. Studies are still needed to clarify the influence of these polymorphisms on hepatic steatosis and degree of fibrosis among individuals diagnosed with chronic hepatitis C